title: Muscle pathology in 31 patients with calpain 3 gene mutations..
abstract: OBJECTIVE
  At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteo-lytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A.
  
  
  METHODS
  In an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation.
  
  
  RESULTS
  In all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation.
  
  
  CONCLUSIONS
  These findings may be helpful in establishing diagnostic strategies in LGMD.
authors.affiliation: Centre de Référence des Maladies Neuromusculaires Nantes/Angers, Service de Neurologie, CHU d'Angers 4, rue Larrey, France. anadpak@gmail.com
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Nadaj-Pakleza
authors.forename: M
authors.initials: M
authors.lastname: Dorobek
authors.forename: K
authors.initials: K
authors.lastname: Nestorowicz
authors.forename: B
authors.initials: B
authors.lastname: Ryniewicz
authors.forename: E
authors.initials: E
authors.lastname: Szmidt-Sałkowska
authors.forename: A M
authors.initials: AM
authors.lastname: Kamińska
mesh_terms: D000293:Adolescent; D001706:Biopsy; D015153:Blotting, Western; D001921:Brain / Q000473:pathology* / Q000601:surgery*; D002154:Calpain / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology*; D009154:Mutation / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain